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Prepared for the L aboratory for P roduct and P rocess D esign Created by Eric Lueshen

Prepared for the L aboratory for P roduct and P rocess D esign Created by Eric Lueshen Advisor: Andreas A. Linninger Presented on September 22, 2011. Magnetically Targeted Drug Delivery to the Brain & Central Nervous System. Outline of Recent Research.

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Prepared for the L aboratory for P roduct and P rocess D esign Created by Eric Lueshen

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  1. Prepared for the Laboratory for Product and Process Design Created by Eric Lueshen Advisor: Andreas A. Linninger Presented on September 22, 2011 Magnetically Targeted Drug Delivery to the Brain & Central Nervous System

  2. Outline of Recent Research • Successful intrathecal (IT) guidance experiments • Unsuccessful MNP guidance through gel experiments • Pharmacokinetics paper #2 resubmitted • NSF drug delivery grant annual project report • Researched methods for lowering nanoparticle agglomeration • Animal protocols: • IT guidance of MNPs in rats • Vasculature stent experiments in rats

  3. Animal Protocol #1 IT Guidance of MNPs in Rats L5-L6 L5-L6

  4. Animal Protocol #1 IT Guidance of MNPs in Rats L5-L6 • Anesthetize the rat • Position rat in stereotax such that lumbar spine is flexed • Shave and prep skin • Cut dorsal midline incision immediately rostral to pelvic girdle • Advance 0.5” 30G needle between L5/L6 into subarachnoid space surrounding the cauda equina • Use vertebral processes and the angio for guidance L5-L6

  5. Animal Protocol #1 IT Guidance of MNPs in Rats • Position magnet above mid-upper thoracic spine • Infuse core-shell MNPs at L5/L6 • Magnetite core • Gold shell (visible in angio) • Visualize experiment with angiography machine • See if MNPs are halted by external magnetic field, thus preventing them from entering the brain L5-L6 L5-L6

  6. Intrathecal Plan for Upcoming Weeks • Finish writing IT animal protocol • Synthesize Fe3O4-Au MNPs • Run calibration experiment in angio • Determine best method to reduce agglomeration

  7. Animal Protocol #2 Vasculature Stent • What is a stent used for? • What does a stent look like? • Examples of two types of stents

  8. Animal Protocol #2 Vasculature Stent

  9. Animal Protocol #2 Vasculature Stent • Coat wire with CD34 endothelial progenitor cell (EPC) antibody • Insert wire into rat carotid artery 1) 2) • Functionalize MNPs with CD34-EPC antibody • Use external magnet to halt antibody-MNPs in rat carotid artery • See if more CD34 EPCs gather & grow around where antibody-wire and/or antibody-MNPs are located

  10. Vasculature Stent Plan for Upcoming Weeks • Determine which antibody to use • Research how to functionalize antibody onto MNPs and nitinol wire • Clarify specifics of experiment & analysis methods • Finish writing draft of vasculature stent animal protocol

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